Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells

Flores Pérez, Ali y Marchat, Laurence A. y Rodríguez Cuevas, Sergio y Bautista, Verónica Piña y Fuentes Mera, Lizeth y Romero Zamora, Diana y Maciel Dominguez, Anabel y De la Cruz, Olga Hernández y Fonseca Sánchez, Miguel y Ruíz García, Erika y La Vega, Horacio Astudillo de y López Camarillo, César (2016) Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells. BMC Cancer, 16 (1). ISSN 1471-2407

[img]
Vista previa
Texto
17.pdf - Versión Publicada
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Vista previa

Resumen

Background: Aberrant expression of microRNAs has been associated with migration of tumor cells. In this study, we aimed to investigate the biological significance of miR-944 whose function is unknown in breast cancer. Methods: MiR-944 expression in breast cancer cells and tumors was evaluated by Taqman qRT-PCR assays. Transcriptional profiling of MDA-MB-231 cells expressing miR-944 was performed using DNA microarrays. Cell viability, migration and invasion were assessed by MTT, scratch/wound-healing and transwell chamber assays, respectively. The luciferase reporter assay was used to evaluate targeting of SIAH1, PTP4A1 and PRKCA genes by miR-944. SIAH1 protein levels were measured by Western blot. Silencing of SIAH1 gene was performed by RNA interference using shRNAs. Results: Our data showed that miR-944 expression was severely repressed in clinical specimens and breast cancer cell lines. Suppression of miR-944 levels was independent of hormonal status and metastatic potential of breast cancer cells. Gain-of-function analysis indicated that miR-944 altered the actin cytoskeleton dynamics and impaired cell migration and invasion. Genome-wide transcriptional profiling of MDA-MB-231 cells that ectopically express miR-944 showed that 15 genes involved in migration were significantly repressed. Notably, luciferase reporter assays confirmed the ability of miR-944 to bind the 3´UTR of SIAH1 and PTP4A1 genes, but not PRKCA gene. Congruently, an inverse correlation between miR-944 and SIAH1 protein expression was found in breast cancer cells. Moreover, SIAH1 was upregulated in 75 % of miR-944-deficient breast tumors. Finally, SIAH1 gene silencing by RNA interference significantly impaired cell migration of breast cancer cells. Conclusions: Our results pointed out that miR-944 is a novel upstream negative regulator of SIAH1 and PTP4A1 genes and provided for the first time evidence for its functional role in migration and invasion of breast cancer cells. They also suggest that miR-944 restoration may represent a potential strategy for breast cancer therapy.

Tipo de elemento: Article
Palabras claves no controlados: Breast cancer, miR-944, Migration, Invasion, Actin cytoskeleton, SIAH1, PTP4A1
Usuario depositante: Editor Repositorio
Creadores:
CreadorEmailORCID
Flores Pérez, AliNO ESPECIFICADONO ESPECIFICADO
Marchat, Laurence A.NO ESPECIFICADONO ESPECIFICADO
Rodríguez Cuevas, SergioNO ESPECIFICADONO ESPECIFICADO
Bautista, Verónica PiñaNO ESPECIFICADONO ESPECIFICADO
Fuentes Mera, LizethNO ESPECIFICADONO ESPECIFICADO
Romero Zamora, DianaNO ESPECIFICADONO ESPECIFICADO
Maciel Dominguez, AnabelNO ESPECIFICADONO ESPECIFICADO
De la Cruz, Olga HernándezNO ESPECIFICADONO ESPECIFICADO
Fonseca Sánchez, MiguelNO ESPECIFICADONO ESPECIFICADO
Ruíz García, ErikaNO ESPECIFICADONO ESPECIFICADO
La Vega, Horacio Astudillo deNO ESPECIFICADONO ESPECIFICADO
López Camarillo, CésarNO ESPECIFICADONO ESPECIFICADO
Fecha del depósito: 11 Sep 2018 18:30
Última modificación: 22 Abr 2021 01:15
URI: http://eprints.uanl.mx/id/eprint/14766

Actions (login required)

Ver elemento Ver elemento

Downloads

Downloads per month over past year